Colon carcinogenesis in shrews by intrarectal infusion of N-methyl-N-nitrosourea

Intrarectal infusion of a 0.15 ml solution containing 1.5 mg or 0.5 mg of N-methyl-N-nitrosourea (MNU) was given to female shrews from 6 weeks of age. Fifteen shrews were given 16 doses of 1.5 mg MNU administered biweekly (group 1), 15 shrews were given 24 doses of 0.5 mg MNU weekly (group 2), and four untreated shrews served as controls (group 3). Moribund shrews were killed during the course of the experiment and all remaining animals were killed at 37 weeks of age and terminated the experiment. The mean age when killed was 30.8 weeks in group 1 and 36.2 weeks in group 2. All autopsied shrews in group 1 and group 2, 13 shrews each, had colon cancers, and there were a few small intestinal cancers and uterine squamous cell carcinomas, while no tumors were seen in the untreated shrews. The colonic lesions were of both exophytic and endophytic type with a variety of histologies and depths of invasion. Mesenteric lymph node metastasis was seen in 31% (4/13) of group 1 and 23% (3/13) of group 2. Thus, MNU, a colonotrophic carcinogen in rodents, also induced colon cancer in shrews in the present study.